Medical device balloons with improved strength properties and processes for producing the same

ABSTRACT

A tubular parison for forming a medical device balloon. The parison is formed of a polymeric material, for instance a thermoplastic elastomer. The parison has an elongation at break which is not more than 80% of the elongation of the bulk polymeric material. The elongation of the parison is controlled by altering extrusion conditions. Balloons prepared from the parisons provide higher wall strength and/or higher inflation durability than balloons prepared from conventional parisons of the same material.

BACKGROUND OF THE INVENTION

Medical devices comprising catheter balloons are used in an increasinglywidening variety of applications including vascular dilatation, stentdelivery, drug delivery, delivery and operation of sensors and surgicaldevices such as blades, and the like. The desired physical propertyprofile for the balloons used in these devices vary according to thespecific application, but for many applications a high strength robustballoon is necessary and good softness and trackability properties arehighly desirable.

Commercial high strength balloons having wall strengths in excess of20,000 psi, have been formed of a wide variety of polymeric materials,including PET, nylons, polyurethanes and various block copolymerthermoplastic elastomers. U.S. Pat. No. 4,490,421, Levy and U.S. Pat.No. 5,264,260, Saab describe PET balloons. U.S. Pat. No. 4,906,244,Pinchuk et al, and U.S. Pat. No. 5,328,468, Kaneko, describe polyamideballoons. U.S. Pat. No. 4,950,239, Gahara, and U.S. Pat. No. 5,500,180,Anderson et al describe balloons made from polyurethane blockcopolymers. U.S. Pat. No. 5,556,383, Wang et al and U.S. Pat. No.6,146,356, Wang et al, describes balloons made frompolyether-block-amide copolymers and polyester-block-ether copolymers.U.S. Pat. No. 6,270,522 Simhambhatla, et al, describes balloons madefrom polyester-block-ether copolymers of high flexural modulus. U.S.Pat. No. 5,344,400, Kaneko, describes balloons made from polyarylenesulfide. All of these balloons are produced from extruded tubing of thepolymeric material by a blow-forming radial expansion process. U.S. Pat.No. 5,250,069, Nobuyoshi et al, U.S. Pat. No. 5,797,877, Hamilton et al,and U.S. Pat. No. 5,270,086, Hamlin, describe still further materialswhich may be used to make such balloons.

Different balloon materials provide different properties. In general,materials with high elongation and low flexural modulus give relativelygreater resistance to pin hole formation and to winging upon deflationand also provide better trackability through body lumens, but suchmaterials tend to give balloons with lower burst strengths and higherdistensibility. Conversely, polymer materials with relatively hightensile strengths and hardness tend to give balloons with low distensionand high burst strengths, but at a sacrifice of susceptibility to pinholing, winging and/or loss of trackability.

A variety of blow forming techniques have been utilized. The extrudedparison may be radially expanded as is into a mold or by free-blowing.Alternatively, the parison may be pre-stretched longitudinally beforeexpansion or reformed in various ways to reduce thickness of the ballooncone and waist regions prior to radial expansion. The blowing processmay utilize pressurization under tension, followed by rapid dipping intoa heated fluid; a sequential dipping with differing pressurization; apulsed pressurization with compressible or incompressible fluid, afterthe material has been heated. Heating may also be accomplished byheating the pressurization fluid injected into the parison. Examples ofthese techniques may be found in the patent documents already mentionedor in U.S. Pat. No. 4,963,313, Noddin et al, U.S. Pat. No. 5,306,246Sahatjian, U.S. Pat. No. 4,935,190, Tennerstedt, U.S. Pat. No.5,714,110, Wang et al.

Following blow-forming the balloons may be simply cooled, heat set at astill higher pressure and/or temperature or heat shrunk at anintermediate pressure and/or temperature, relative to the blow formingtemperature and pressure. See U.S. Pat. No. 5,403,340, Wang et al, EP540858 Advanced Cardiovascular Systems, Inc., WO 98/03218, Scimed LifeSystems.

Thus a great deal of attention has been paid to blow forming processingconditions and to balloon materials. Less attention has been paid toextrusion conditions for preparing the polymer tubing used as theparison: In general, dry polymer has been used. It has been recognizedthat a single die can be used to produce different tubing diameters byvarying the draw down ratio, but, at least since-the advent of PETballoons, relatively low draw down ratios have been recommended toprovide an amorphous state and thereby facilitate the subsequentblow-forming step. See S. Levy, “Improved. Dilatation CatheterBalloons,” J. Clinical Engineering, Vol. 11, No. 4, July-August 1986,291-295, at p 293.

Balloons made from thermoplastic elastomers are desirable because theyare relatively soft and robust, have good trackability and still provideadequate strength for many applications. However, as demands for balloonperformance have increased, a need has arisen to find a way to improvewall strength of thermoplastic elastomer balloons without requiringstill further increases in hoop ratios, and/or to provide more robustballoons without sacrificing wall strength.

SUMMARY OF THE INVENTION

The present invention is directed to methods of forming balloons andparisons therefor.

Surprisingly, it has been found that improved balloon properties can beobtained by controlling the parison extrusion in a manner whichrestricts the elongation of the parison material in the longitudinaldirection. In one aspect the invention is a method of extruding aparison useful for forming a medical balloon by a radial expansionprocess, the method comprising extruding the parison in a manner whichprovides the parison material with an elongation which is not more than80% of the elongation of the bulk material. In another aspect theinvention is a method of extruding a parison, the method comprisingextruding a tube of polymeric material to form the tube at across-sectional area draw down ratio of about 8 or higher.

In still another aspect, the invention is directed to improved balloonscharacterized by a particular high strength property; to medical devicescomprising such balloons; and to surgical procedures employing suchdevices. A particular embodiment is a balloon formed from athermoplastic elastomer and having a wall strength of at least 34,000psi, especially at least 37,000 psi, in pre-sterilized condition. Afurther embodiment is such a balloon, in post-sterilized condition,having a wall strength of 32,000 psi or more.

Further aspects of the invention are described in the following detaileddescription of the invention or in the claims.

DETAILED DESCRIPTION OF THE INVENTION

All published documents, including all US patent documents, mentionedanywhere in this application are hereby expressly incorporated herein byreference in their entirety. Any copending patent applications,mentioned anywhere in this application are also hereby expresslyincorporated herein by reference in their entirety.

It has been found that the distention and the burst pressure of aballoon are affected by the elongation properties of the extrudedparison, as well as by the hoop ratio and the tube wall thickness. It isbelieved the elongation affects the balloon properties through itseffect on the balloon wall thickness. Thus, for a given hoop ratio andtube size, as parison elongation decreases, the balloon wall thicknessincreases, the balloon distention decreases and the burst pressureincreases.

Thus, while an increase in the hoop strength and modulus comes at theexpense of thinner balloon walls, which can increase distention anddecrease burst pressure, it is also possible to extrude tubes with lowerelongation to break. This allows one to provide even stronger walls thanwere previously been obtained with a given polymer. Alternatively, theinvention can allow one to thicken the balloon wall, while affecting thehoop strength and distension very little, thereby obtaining a balloonwhich is more suited to stent or other surgical device deliveryoperations.

In one aspect the invention involves modifying the parison processing soas to provide the parison material with an elongation which is not morethan 80% of the elongation of the bulk material. In particular, when 3inch length of the extruded tube is stretched until it breaks, thelength of the tube when it breaks will correspond to a percentageincrease which is not more than 80% of the elongation value obtained bydetermining elongation of the bulk material per ASTM D-638. In someembodiments the parison is processed so as to provide the parisonmaterial with an elongation which is not more than 70% of the elongationof the bulk material, and in still others the parison elongation is lessthan 60% of the elongation of the bulk material.

The parison processing techniques described herein, alone or incombination can provide balloon wall strength improvements of as much as10-25% over those obtainable in their absence, for non-sterilizedballoons. Sterilization, depending on the technique chosen, may reducethis benefit somewhat. The invention may be used with any known balloonmaterials, however high strength thermoplastic elastomers are preferred,especially polyamide polyether block copolymers, includingpolyamide/polyether/polyesters such as sold under the PEBAX trademark,in particular PEBAX 7033 and PEBAX 7233; polyester/polyether blockcopolymers such as sold under the HYTREL and ARNITEL trademarks, inparticular ARNITEL EM 740 and HYTREL 8238; and polyurethane blockcopolymers such as PELLETHANE 2363-75D. The parison may be extruded as asingle layer or in multiple layers, for instance 3, 5, 7, or even morealternating layers of PEBAX 7033 and Pebax 7233. Blends of such polymersmay also be used.

Parison elongation may be controlled by varying one or more of thefollowing extrusion parameters:

Extrusion Temperature:

The temperature at the extrusion head, die temperature, is loweredrelative to the temperature in the extruder barrel.. Heat loss beginseven as the material is passing through the die head. The resultingtubing has a higher degree of crystallization. In general the die headtemperature reduction should be about 5 to about 50° F., suitably 10° F.to 40° F., and preferably about 20-30° F. below the barrel temp.

Draw Down Ratio:

Die configuration, extruder pressure and/or line speeds can be adjustedto provide a cross-sectional area draw down ratio in excess of 5:1.Ratios as high as 17:1 have been employed, and even higher ratios may beadvantageous because they reduce extruder pressure demands. Typicallythe draw down ratios will be in the range of about 8:1 to about 17:1.

Quench Time:

Decreasing the gap between the extrusion head and the cooling bath tankcan also lower parison elongation by shortening the quench time. Quenchtime can also be shortened by increasing the line speed.

Bath Temperature:

Maintaining the cooling bath at a lower temperature also can lower theelongation of the parison.

A surprising benefit of at least some embodiments of the invention isthat balloons prepared from parisons of the invention have improvedresistance to repeat inflation bursts versus controls utilizing the samepolymer, but prepared using typical extrusion parameters for commercialballoons. The improvement may permit three times, or even more, thenumber of inflations to rated pressure, compared to the controls.

The invention is illustrated by the following non-limiting examples.

EXAMPLES

In the following examples the following abbreviations are used.

-   Ex Example No. Alphabetic series are comparative, numeric series are    invention examples.-   OD Outer diameter, as extruded.-   Die temp Extruder die zone temperature in degrees Fahrenheit. The    extruder barrel was kept at 395° F. in these examples.-   Line speed Speed in feet/min of the puller.-   DDR Draw down ratio of the cross-sectional area from extrusion head    opening to final tube dimensions. DDR=[(Die ID)²−(Tip OD)²]/[(Tubing    OD)−(Tubing ID)2]-   Elong@ break Given as percentage elongation determined on a 3″ long    extruded tube which is stretched to break.-   Balloon 2x wall Thickness in inches of the balloon double wall as    measured with a micrometer.-   Hoop Hoop ratio determined as balloon OD (mold diameter)/parison ID    (as extruded).-   Distension The change in diameter as a % of start diameter for the    stated ranges of 6:12 (6 atm to 12 atm) and 12:18 (12 atm to 18 atm)    inflation pressure.-   Burst Pressure in psi at which the balloon burst-   Burst strength Wall strength at burst as calculated by the equation:    T _(s) =PD/2t    -   where: T_(s) is the wall tensile strength;-   P is the balloon burst pressure;-   D is the nominal diameter of the balloon; and-   t is the wall thickness.

All values are averages of at least 6 balloons. Balloon blowingconditions used the same times, temperatures and sequences, except whereindicated.

All data is for balloons having a nominal diameter of 3.0 mm at 6 atm.The balloons were made from PEBAX 7033. The published elongation valuefor the bulk polymer, per ASThM D-638, is 400%. The balloons were madefrom conventionally extruded parisons using a very high hoop ratio and astep-wise dipping process similar to that described in Wang et al,Example 3, U.S. Pat. No. 5,714,110. A typical program is as follows:Program: bath at 95° C. (1) pressure to 100 psi tension to 50 g dip to D8 seconds hold at D 6 seconds (2) pressure to 450 psi tension to 20 gdip to C 4 sec hold at C 6 seconds (3) pressure to 550 psi tension to200 g dip to B 20 sec hold at B 6 secondswhere D, C and B are locations, as described in U.S. Pat. No. 5,714,110.The parison formation conditions and formed balloon results aredescribed in Table 1. Die configuration was not varied-between examples.Tank gaps, die temperatures and speeds were varied as needed to obtainparison elongation targets. Extruder pressure was not independentlycontrolled and varied as a result of changing these conditions.

Table 1 provides an example of a balloon formed using conventional tubeprocessing at a high hoop ratio. TABLE 1 Control Elong Tube Tube DieLine @ Balloon Distension Distension Burst Ex ID OD Temp Speed DDR break2× wall Hoop 6:12 12:18 Burst Strength A .0177 .0321 395 24 3.5 367.00116 6.9 5.6 4.4 301 31056

The elongation at breaks of this parison corresponds to about 91% of thepublished value for the bulk polymer.

Table 2 gives the results of the same balloon wall thickness made inaccordance with the invention by increasing the DDR. The increased drawdown ratio reduced the elongation of this tube to about 48% of thepublished elongation value. TABLE 2 High Draw Down Elong Tube Tube DieLine @ Balloon Distension Distension Burst Ex ID OD Temp Speed DDR break2× wall Hoop 6:12 12:18 Burst Strength 1 .0176 .0310 395 50 12.1 1900.00118 6.9 5.4 4.5 331 34411

Table 3 shows extrusion parameters and balloon property results when,after extrusion, the parison was modified by one of the following stepsbefore it was blow-formed into a balloon.

Example 2

A freeze spray process was used to selectively reduce parison cone andwaists as per Example 1 of U.S. Pat. No. 5,807,520.

Example 3

Cones and waists were selectively reduced by a grinding and neckingprocess which did not stretch the body-forming portion of the parison.Similar to Example 2, first paragraph of PCT/US01/26140, filed Aug. 22,2001, attorney docket no S63.3-9928, corresponding to U.S. applicationSer. No. 09/672330 filed Sep. 28, 2000.

Example 4

the entire parison was stretched longitudinally at ambient temperatureunder internal pressurization to maintain ID at the extruded dimension(±4%) at a stretch ratio 3x, where x is starting length. See control inExample 1 of PCT/US01/26140. TABLE 3 Parison Modifications Elong TubeTube Die Line @ Balloon Distension Distension Burst Ex ID OD Temp SpeedDDR break 2× wall Hoop 6:12 12:18 Burst Strength 2 0.176 .0290 395 5012:1 193 .00105 6.9 5.3 4.7 309 36101 3 .0176 .0290 395 50 12:1 193.00098 6.9 4.8 4.8 297 37423 4 .0176 .0290 395 50 12:1 193 .00097 6.94.9 4.7 300 37577

In examples 2-4, the burst pressure in all cases was comparable to thecontrol balloon, but with thinner walls so the wall strength is muchimproved over the control balloon.

Example 5

Balloons were made using PEBAX 7033 parisons stretched at ambienttemperature at a stretch ratio of 1.5x and a hoop ratio of 7.0.Parisons, extruded to keep the parison elongation at break above 80% ofthe published elongation of the polymer, were used as controls.Parisons, extruded to provide a parison elongation at break of about 50%or less of the published elongation of the polymer, were prepared asinvention examples. The balloons were inflated to 211 psi and deflatedrepeatedly. Four balloons were present in each group. The controlballoon group, on average, failed at about 80 repeats. All of theballoons of the invention group survived 235 repeats without failure, atwhich point the test was discontinued.

The above examples and disclosure are intended to be illustrative andnot exhaustive. These examples and description will suggest manyvariations and alternatives to one of ordinary skill in this art. Allthese alternatives and variations are intended to be included within thescope of the claims, where the term “comprising” means “including, butnot limited to”. Those familiar with the art may recognize otherequivalents to the specific embodiments described herein whichequivalents are also intended to be encompassed by the claims. Further,the particular features presented in the dependent claims can becombined with each other in other manners within the scope of theinvention such that the invention should be recognized as alsospecifically directed to other embodiments having any other possiblecombination of the features of the dependent claims. For instance, forpurposes of claim publication, any dependent claim which follows shouldbe taken as alternatively written in a multiple dependent form from allprior claims which possess all antecedents referenced in such dependentclaim if such multiple dependent format is an accepted format within thejurisdiction (e.g. each claim depending directly from claim 1 should bealternatively taken as depending from all previous claims). Injurisdictions where multiple dependent claim formats are restricted, thefollowing dependent claims should each be also taken as alternativelywritten in each singly dependent claim format which creates a dependencyfrom a prior antecedent-possessing claim other than the specific claimlisted in such dependent claim below.

1. A method of making a parison for forming a medical device balloon,the method comprising extruding a tube of polymeric material to form thetube, wherein the extrusion is controlled to provide the extruded tubewith an elongation at break which is not more than 80% of the elongationat break of the bulk polymeric material.
 2. A method as in claim 1wherein the elongation at break of the extruded tube is not more thanabout 70% of the elongation at break of the bulk polymeric material. 3.A method of making a parison for forming a medical device balloon, themethod comprising extruding a tube of polymeric material to form thetube, the extrusion having a draw down ration of about 8 or higher.
 4. Amethod of making a parison for forming a medical device balloon, themethod comprising extruding a tube of polymeric material from anextruder having a barrel where the mixture is kept in molten state at abarrel temperature and a die zone where the molten material is pushedthrough a die to form the tube, wherein the die zone is kept at atemperature at least 5° F. below the barrel temperature.
 5. A method asin claim 4 wherein said die zone temperature is 10-40° F. below thebarrel temperature.
 6. A method as in claim 4 wherein said die zonetemperature is 20-30° F. below the barrel temperature. 7-24. (canceled)